High-Risk HPV, Biomarkers, and Outcome in Matched Cohorts of Head and Neck Cancer Patients Positive and Negative for HIV

• Type of Material: Article
• Authors: Heather M. Walline, University of Michigan; Thomas E. Carey, University of Michigan; Christine M. Goudsmit, University of Michigan; Emily L. Bellile, University of Michigan; Gypsyamber D'Souza, Johns Hopkins University; Lisa A. Peterson, University of Michigan; Jonathan B. McHugh, University of Michigan; Sara I. Pai, Johns Hopkins University; J. Jack Lee, MD Anderson Cancer Center; Dong M Shin, Emory University; Robert L. Ferris, University of Pittsburgh
• Language: English
• Date: 2017-02-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2016 AACR.
• Final Published Version (URL): http://dx.doi.org/10.1158/1541-7786.MCR-16-0255
• Title of Journal or Parent Work: Molecular Cancer Research
• ISSN: 1541-7786
• Volume: 15
• Issue: 2
• Start Page: 179
• End Page: 188
• Grant/Funding Information: This work was supported by the NCI HIV Supplement to the Head and Neck SPORE Consortium.; This study was also supported by grants to the following institutions: ARRA: University of Michigan: P50 CA097248 R01 CA194536 (to T. Carey); University of Michigan Cancer Center Core Grant P30 CA46592; MD Anderson: 5P50 CA097007; University of Pittsburgh: P50 CA097190; Johns Hopkins University, P50 DE019032 and 3P50 DE019032-14S2; Emory University: P50 CA128613, R01 DE021395 (to G. D'Souza), P50 CA128613, and P50 CA128613-02S1.
• Keywords: Cell Biology; SQUAMOUS-CELL CARCINOMA; UNITED-STATES; P16; SURVIVAL; Life Sciences & Biomedicine; Science & Technology; ANTIRETROVIRAL THERAPY; CERVICAL-CANCER; Oncology; INDIVIDUALS; DISEASE; HUMAN-PAPILLOMAVIRUS INFECTION; OROPHARYNGEAL CANCER
• Research Categories: Health Sciences, Public Health; Biology, Biostatistics; Health Sciences, Epidemiology

Abstract

In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR, and in situ hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells. The HNSCC cohort included 41 HIV-positive cases and 41 HIV-negative controls. Tumors from 11 of 40 (28%) cases, and 10 of 41 (24%) controls contained hrHPV. p16 expression, indicative of E7 oncogene activity, was present in 10 of 11 HPV-positive cases and 7 of 10 HPV-positive controls. Low p16 and high TP53 expression in some HPV-positive tumors suggested HPV-independent tumorigenesis. Survival did not differ in cases and controls. RB expression was significantly associated with poor survival (P = 0.01). High TP53 expression exhibited a trend for poorer survival (P = 0.12), but among cases, association with poor survival reached statistical significance (P = 0.04). The proportion of HPV-positive tumors was similar, but the heterogeneity of HPV types was higher in the HIV-positive cases than in HIV-negative controls. High RB expression predicted poor survival, and high TP53 expression was associated with poorer survival in the HIV-positive cases but not HIV-negative controls.